As anti-obesity agents or anti-diabetic agents belonging to a new category of agents without using insulin, 1-phenyl-2-(2-phenyl-1-methylethyl)amino!ethanol derivatives are noted since the derivatives act selectively on a .beta..sub.3 -receptor in vivo, thus having extremely low side effects. Pharmacological studies on the 1-phenyl-2-(2-phenyl-1-methylethyl)amino!ethanol derivatives have revealed that the .beta..sub.3 -action substantially depends on (R,R)-enantiomers thereof (see J. Med. Chem., 35, 3081 (1992), and U.S. Pat. No. 5,061,727). For example, the above-mentioned U.S. Patent discloses that an (R,R)-5-2-2-(3-chlorophenyl)-2-hydroxyethyl!amino!propyl!-1,3-benzodiox ole-2,2-dicarboxylic acid disodium salt has a higher activity than the corresponding (S,S)-enantiomer by a factor of 47.
For the production of an optically active 1-phenyl-2-(2-phenyl-1-methylethyl)amino!ethanol derivative, there is known an optical resolution of a racemic form or a racemate, or an asymmetric synthesis.
For example, the above mentioned U.S. Pat. No. 5,061,727 discloses a method of producing an (R,R)-1-phenyl-2-(2-phenyl-1-methylethyl)amino!ethanol derivative which comprises (1) allowing a racemic 2-amino-1-phenylethanol derivative to react with a phenylacetone derivative and sodium cyanoborohydride to produce a mixture of four species of optical isomers of a 1-phenyl-2-(2-phenyl-1-methylethyl)amino!ethanol derivative, (2) isolating and removing an (R,S)-isomer and an (S,R)-isomer from the mixture, and (3) optically resoluting an (R,R)-isomer and an (S,S)-isomer by a diastereomer method. According to this method, however, it is necessary to isolate and purify only the (R,R)-isomer from the mixture of the four species of optical isomers, therefore, the processes are complicated and the yield is decreased. Further, since large quantities of raw materials are required, the method is also disadvantageous in economical factor.
The U.S. Patent and the Journal of Medicinal Chemistry as mentioned above disclose a method allowing an (R)-3-chlorostyrene oxide derivative to react with an (R)-1-methyl-2-phenylethylamine derivative. The (R)-1-methyl-2-phenylethylamine derivative used as a raw material or reactant in the method, however, has a strong antihypnotic or arousal action and it requires a particular attention when handled, therefore is not suited for a use in commercial production. Further, a lot of steps or processes are required to obtain the above-mentioned two reactants. For instance, the (R)-3-chlorostyrene oxide derivative is prepared from an acetophenone derivative through three steps, that is, chlorination, asymmetric reduction and epoxidation, and the (R)-1-methyl-2-phenylethylamine derivative is prepared from L-DOPA through six steps, namely, introduction of a protective group into an amino group, esterification, reduction of the resulting ester, converting a hydroxyl group to a mesyloxy group, removal of the protective group and reduction.